Aqueous olefin metathesis: recent developments and applications

Abstract

Olefin metathesis is one of the most powerful C-C double-bond-forming reactions. Metathesis reactions have had a tremendous impact in organic synthesis, enabling a variety of applications in polymer chemistry, drug discovery and chemical biology. Although challenging, the possibility to perform aqueous metatheses has become an attractive alternative, not only because water is a more sustainable medium, but also to exploit biocompatible conditions. This review focuses on the progress made in aqueous olefin metatheses and their applications in chemical biology.

Keywords: aqueous catalysis; artificial metalloenzymes; chemical biology; green chemistry; olefin metathesis; ruthenium catalysts; stapled peptides.

Scheme 1

Most common metathesis reactions. Ring-opening metathesis polymerization (ROMP), acyclic diene metathesis (ADMET), ring-closing metathesis (RCM), ring-opening metathesis (ROM), and cross-metathesis (CM).

Scheme 2

Catalytic cycle for metathesis proposed by Chauvin.

Figure 1

Some of the most representative catalysts for aqueous metathesis. a) Well-defined ruthenium catalysts. b) Catalysts bearing ammonium tags. c) PEG-tethered catalysts.

Scheme 3

First aqueous ROMP reactions catalyzed by ruthenium(III) salts.

Scheme 4

Degradation pathway of first generation Grubbs catalyst (G-I) in methanol.

Scheme 5

Synthesis of Blechert-type catalysts 19 and 20.

Figure 2

Chemical structure and components of amphiphilic molecule PTS and derivatives.

Scheme 6

RCM of selected substrates in the presence of the surfactant PTS. Conditions^a: The reaction was carried out at 60 °C for 24 hours.

Scheme 7

RCM reactions of substrates 31 and 33 with the encapsulated G-II catalyst.

Scheme 8

Living ROMP of norbornene derivatives 35 and 36 with phosphine-based catalysts bearing quaternary ammonium tags 1 and 2.

Scheme 9

Synthesis of water-soluble catalysts 3 and 4 bearing quaternary ammonium tags.

Scheme 10

In situ formation of catalyst 5 bearing a quaternary ammonium group.

Scheme 11

Catalyst recycling of an ammonium-bearing catalyst.

Scheme 12

Removal of the water-soluble catalyst 12 through host–guest interaction with silica-gel-supported β-cyclodextrin.

Scheme 13

Selection of artificial metathases reported by Ward and co-workers (ArM 1 based on biotin–(strept)avidin technology and ArM 2 based on dative anchoring to hCAII).

Figure 3

In vivo metathesis with an artificial metalloenzyme based on the biotin–streptavidin technology.

Scheme 14

Artificial metathase based on covalent anchoring approach. α-Chymotrypsin interacts with catalyst 66 through supramolecular interactions followed by covalent nucleophilic attack to afford ArM 3.

Scheme 15

Assembling an artificial metathase (ArM 4) based on the small heat shock protein from M. Jannaschii (MjHSP). The protein structure is based on the atomic coordinates in PDB entry 1SHS.

Scheme 16

Artificial metathases based on cavity-size engineered β-barrel protein nitrobindin (NB4exp). The HG-type catalysts 69, 70 and 71 are located inside nitrobindin to afford ArM 5, ArM 6 and ArM 7.

Scheme 17

Artificial metathase based on cutinase (ArM 8) and resulting metathesis activities.

Scheme 18

Site-specific modification of proteins via aqueous cross-metathesis. The protein structure is based on the atomic coordinates in PDB entry 1NDQ.

Scheme 19

a) Allyl homocysteine (Ahc)-modified proteins as CM substrates. b) Incorporation of Ahc in the Fc portion of IgG in human cells (HEK 293T) and CM reaction with 84.

Scheme 20

On-DNA cross-metathesis reaction of allyl sulfide 99.

Scheme 21

Preparation of BODIPY-containing profluorescent probes 102 and 104.

Scheme 22

Metathesis-based ethylene detection in live cells.

Scheme 23

First example of stapled peptides via olefin metathesis.